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Research Article

Angiotensin II type 1 receptor autoantibody blockade improves cerebral blood flow autoregulation and hypertension in a preclinical model of preeclampsia

, , , , , , , & show all
Pages 451-460 | Received 27 May 2020, Accepted 01 Oct 2020, Published online: 29 Oct 2020
 

ABSTRACT

Introduction:Women with preeclampsia (PE) and reduced uterine perfusion pressure (RUPP) pre-clinical rat model of PE have elevated angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA) and cerebrovascular dysfunction.

Methods:Sprague Dawley rats had RUPP surgery with/without AT1-AA inhibitor (‘n7AAc’144 μg/day) osmotic minipumps. Mean arterial pressure (MAP), CBF autoregulation, blood brain barrier (BBB) permeability, cerebral edema, oxidative stress, and eNOS were assessed.

Results:‘n7AAc’ improved MAP, restored CBF autoregulation, prevented cerebral edema, elevated oxidative stress, and increased phosphorylated eNOS protein in RUPP rats.

Conclusion:Inhibiting the AT1-AA in placental ischemic rats prevents hypertension, cerebrovascular dysfunction, and improves cerebral metabolic function.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes

1. Groups are normal pregnant, Reduced Uterine Perfusion Pressure (RUPP), and RUPP + AT1-AA inhibitor peptide (“n7AAc”). Statistical differences were achieved by using one-way ANOVA with Dunnet’s post hoc analysis.*p < 0.05 vs. NP

2. Groups are normal pregnant, Reduced Uterine Perfusion Pressure (RUPP), and RUPP + AT1-AA inhibitor peptide (“n7AAc”). Statistical differences were achieved by using one-way ANOVA with Dunnet’s post hoc analysis.*p < 0.05 vs. NP

Additional information

Funding

Research Supported primarily byAHA [18CDA34110264 (Cunningham), T32HL105324 (Cunningham & Duncan)], [AHA 19POST34450074, NIH P20GM104357, P01HL051971, 5U54GM115428 (Duncan), P20GM121334, RO1HD067541 (LaMarca), HL138685 (Roman), 050049 (Fan). P20GM104357 (Fan), AG060049 (Fan), and AG057842 (Fan)]. NIH/NIDDK [DK109133 (Williams)]

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